Thiazole-4-carboxaldehyde → HCID 178522001, compound

HRID 1628222Notes

Reaction equation

HRID 1628222 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[C:8]([NH:12][C:13](=[O:23])[C@@H:14]([NH2:22])[CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:9]=[CH:10][CH:11]=2)=[N:2]1.[S:24]1[CH:28]=[C:27]([CH:29]=O)[N:26]=[CH:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[C:8]([NH:12][C:13](=[O:23])[C@@H:14]([NH:22][CH2:29][C:27]3[N:26]=[CH:25][S:24][CH:28]=3)[CH2:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:9]=[CH:10][CH:11]=2)=[N:2]1

Participants

5

Reactant 3

HCID 2763214Thiazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 178511766HCID 178511766, compound

Product 1

HCID 178522001HCID 178522001, compoundYield 25.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S)—N-(3-(1H-pyrazol-3-yl)phenyl)-2-amino-3-phenylpropanamide 12.C (200 mg, 0.65 mmol) in DCM (5 mL) was added thiazole-4-carbaldehyde (73 mg, 0.65 mmol, available from Combi-Blocks). The mixture was stirred for 1 h, then sodium triacetoxyborohydride (207 mg, 0.98 mmol) was added and the mixture stirred for an additional hour at room temperature. The mixture was then concentrated and the crude product purified by reverse phase chromatography (0-100% CH3CN/water+0.5% TFA) to afford (2S)—N-(3-(1H-pyrazol-3-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide 12 as a white solid (66.7 mg, 25% yield). LCMS ESI (pos.) m/e: 404.0 (M+1): 1H NMR (500 MHz, MeOH-D4) δ ppm 9.11 (d, J=1.96 Hz, 1H), 7.82-7.87 (m, 1H), 7.80 (d, J=1.96 Hz, 1H), 7.74 (d, J=2.20 Hz, 1H), 7.51-7.60 (m, 1H), 7.21-7.38 (m, 7H), 6.68 (d, J=2.20 Hz, 1H), 4.50 (d, J=5.38 Hz, 2H), 4.29 (dd, J=9.29, 5.87 Hz, 1H), 3.43 (dd, J=13.45, 5.62 Hz, 1H), 3.27 (dd, J=13.45, 9.29 Hz, 1H).

Workup

  1. stirringthe mixture stirred for an additional hour at room temperature
  2. concentrationThe mixture was then concentrated
  3. customthe crude product purified by reverse phase chromatography (0-100% CH3CN/water+0.5% TFA)

Sources & evidence

ORD record
ord-bdfcd13948c7427cbb0feb46aa2c1c70
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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